Cardiovascular determinants of impaired placental function in women with cardiac dysfunction.

Female heart disease has for a long time been an underrecognized problem in the field of cardiology. With an ever-growing number of these patients getting pregnant, cardiac dysfunction during pregnancy is an increasingly large medical problem. Previous work has shown that maternal heart disease may have an adverse effect on pregnancy outcome in both mother and child. The placenta forms the connection and it is postulated that cardiac dysfunction negatively affects the placenta, and consequently, neonatal outcome. Given the paucity of data in this field, more research on the influence of cardiac (mal)function on placental (mal)function is needed. The present review describes placental function in women with various types of cardiac dysfunction, thereby aiming to provide more insight into possible underlying mechanisms of placental malfunction. Organ dysfunction in patients with heart failure is for an important part based on reduced perfusion and venous congestion. This has been shown in other organs such as kidneys, liver and brain. In pregnant women with cardiac dysfunction, placental dysfunction may follow similar patterns. Moreover, other factors, such as pre-existing hypertension and chronic hypoxia may lead to further impairment of placental function, through abnormal vascular remodeling of the uterine spiral arteries. The pathophysiology of placental dysfunction in pregnant women with cardiac dysfunction may thus be multifactorial. It is therefore important to monitor closely cardiac and placental function in such high-risk pregnancies. Gaining a better understanding of the underlying pathophysiological mechanisms may have important clinical implications in terms of pregnancy counseling, monitoring and outcome.

Reduced right ventricular function on cardiovascular magnetic resonance imaging is associated with uteroplacental impairment in tetralogy of Fallot.

BACKGROUND: Maternal right ventricular (RV) dysfunction (measured by echocardiography) is associated with impaired uteroplacental circulation, however echocardiography has important limitations in the assessment of RV function. We therefore aimed to investigate the association of pre-pregnancy RV and left ventricular (LV) function measured by cardiovascular magnetic resonance with uteroplacental Doppler flow parameters in pregnant women with repaired Tetralogy of Fallot (ToF). METHODS: Women with repaired ToF were examined, who had been enrolled in a prospective multicenter study of pregnant women with congenital heart disease. Clinical data and CMR evaluation before pregnancy were compared with uteroplacental Doppler parameters at 20 and 32 weeks gestation. In particular, pulsatility index (PI) of uterine and umbilical artery were studied. RESULTS: We studied 31 women; mean age 30 years, operated at early age. Univariable analyses showed that reduced RV ejection fraction (RVEF; P = 0.037 and P = 0.001), higher RV end-systolic volume (P = 0.004) and higher LV end-diastolic and end-systolic volume (P = 0.001 and P = 0.003, respectively) were associated with higher uterine or umbilical artery PI. With multivariable analyses (corrected for maternal age and body mass index), reduced RVEF before pregnancy remained associated with higher umbilical artery PI at 32 weeks (P = 0.002). RVEF was lower in women with high PI compared to women with normal PI during pregnancy (44% vs. 53%, p = 0.022). LV ejection fraction was not associated with uterine or umbilical artery PI. CONCLUSIONS: Reduced RV function before pregnancy is associated with abnormal uteroplacental Doppler flow parameters. It could be postulated that reduced RV function on pre-pregnancy CMR (≤2 years) is a predisposing factor for impaired placental function in women with repaired ToF.

Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases.

In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis and the institution of potential preventative measures. We also provide practical hints to identify subsets of the DCM syndrome where aetiology directed management has great clinical relevance.

Pregnancy in women with congenital heart disease.

Congenital heart defects are the most common birth defects. Major advances in open-heart surgery have led to rapidly evolving cohorts of adult survivors and the majority of affected women now survive to childbearing age. The risk of cardiovascular complications during pregnancy and peripartum depends on the type of the underlying defect, the extent and severity of residual haemodynamic lesions and comorbidities. Careful individualized, multi-disciplinary pre-pregnancy risk assessment and counselling, including assessment of risks in the offspring and estimation on long-term outcomes of the underlying heart defect, will enable informed decision making. Depending on the estimated risks, a careful follow-up plan during pregnancy as well as a detailed plan for delivery and postpartum care can reduce the risks and should be made by the multi-disciplinary team.

Contraception and cardiovascular disease.

Contraceptive counselling should begin early in females with heart disease, preferably directly after the start of menstruation. In coming to a decision about the method of contraception, the following issues should be considered: (i) the risk of pregnancy for the mother and the consequences of an unplanned pregnancy; (ii) the risks of the contraceptive method; (iii) failure rates; (iv) the non-contraceptive benefits; (v) the availability; (vi) the individual's preferences; (vii) protection against infection; and (viii) costs. In some women with heart disease, the issues may be complex and require the input of both a cardiologist and an obstetrician (or other feto-maternal expert) to identify the optimal approach. No studies have been performed in women with heart disease to investigate the relative risks and benefits of different contraceptive methods.

Secundum atrial septal defect is associated with reduced survival in adult men.

AIMS: The identification of sex differences in the prognosis of adults with a secundum atrial septal defect (ASD2) could help tailor their clinical management, as it has in other cardiovascular diseases. We investigated whether disparity between the sexes exists in long-term outcome of adult ASD2 patients. METHODS AND RESULTS: Patients with ASD2 classified as the primary defect were selected from the Dutch national registry of adult congenital heart disease. Survival stratified by sex was compared with a sex-matched general population. In a total of 2207 adult patients (mean age at inclusion 44.8 years, 33.0% male), 102 deaths occurred during a cumulative follow-up of 13 584 patient-years. Median survival was 79.7 years for men and 85.6 years for women with ASD2. Compared with the age- and sex-matched general population, survival was lower for male, but equal for female patients (P = 0.015 and 0.766, respectively). Logistic regression analyses showed that men had a higher risk of conduction disturbances (OR = 1.63; 95% CI, 1.22-2.17) supraventricular dysrhythmias (OR = 1.41; 1.12-1.77), cerebrovascular thromboembolic events (OR = 1.53; 1.10-2.12), and heart failure (OR = 1.91; 1.06-3.43). CONCLUSION: In contrast to women, adult men with an ASD2 have worse survival than a sex-matched general population. Male patients also have a greater risk of morbidity during adult life. Sex disparity in survival and morbidity suggests the need for a sex-specific clinical approach towards these patients.

Cardiac function and cardiac events 1-year postpartum in women with congenital heart disease.

BACKGROUND: Pregnancy is increasingly common in women with congenital heart disease (CHD), but little is known about long-term cardiovascular outcome after pregnancy in these patients. We studied the incidence of cardiovascular events 1-year postpartum and compared cardiac function prepregnancy and 1-year postpartum in women with CHD. METHODS: From our national, prospective multicenter cohort study, 172 women were studied. Follow-up with clinical evaluation and echocardiography and NT-proBNP measurement were performed during pregnancy and 12 months postpartum. Cardiovascular events were defined as need for an urgent invasive cardiovascular procedure, heart failure, arrhythmia, thromboembolic events, myocardial infarction, cardiac arrest, cardiac death, endocarditis, and aortic dissection. RESULTS: Cardiovascular events were observed after 11 pregnancies (6.4%). Women with cardiovascular events postpartum had significant higher NT-proBNP values at 20-week gestation (191 [137-288] vs 102.5 [57-167]; P = .049) and 1-year postpartum compared with women without cardiovascular events postpartum (306 [129-592] vs 105 [54-187] pg/mL; P = .014). Women with cardiovascular events during pregnancy were at higher risk for late cardiovascular events (HR 7.1; 95% CI 2.0-25.3; P = .003). In women with cardiovascular events during pregnancy, subpulmonary end-diastolic diameter had significantly increased 1-year postpartum (39.0 [36.0-48.0] to 44.0 [40.0-50.0]; P = .028). No other significant differences were found in cardiac function or size 1-year postpartum compared with preconception values. CONCLUSIONS: Cardiovascular events are relatively rare 1 year after pregnancy in women with CHD. Women with cardiovascular events during pregnancy are prone to develop cardiovascular events 1-year postpartum and have increased subpulmonary ventricular diameter compared with preconception values.

N-terminal pro-B-type natriuretic peptide predicts cardiovascular complications in pregnant women with congenital heart disease.

AIMS: In women with congenital heart disease (CHD), cardiovascular complications during pregnancy are common, but the risk assessment of these patients remains difficult. This study sought to determine the independent role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in addition to other parameters in predicting adverse cardiovascular events during pregnancy in women with CHD. METHODS AND RESULTS: We conducted a national, prospective multicentre cohort study. Follow-up with clinical evaluation and echocardiography and NT-proBNP measurement was performed at 20-week gestation. Adverse cardiovascular events occurred in 10.3% of 213 pregnancies. N-terminal pro-B-type natriuretic peptide levels >128 pg/mL at 20-week gestation, the presence of a mechanical valve, and subpulmonary ventricular dysfunction before conception were independently associated with events [odds ratio (OR) 10.6 (P = 0.039), OR 12.0 (P = 0.016), and OR 4.2 (P = 0.041), respectively]. The negative predictive value of NT-proBNP levels <128 pg/mL was 96.9%. N-terminal pro-B-type natriuretic peptide levels >128 pg/mL at 20 weeks of gestation had an additional value in predicting the occurrence of adverse cardiovascular events on the top of the other identified predictors (area under the curve 0.90 vs. 0.78, P = 0.035). CONCLUSION: Increased NT-proBNP levels at 20 weeks of gestation are an independent risk predictor of cardiovascular events during pregnancy in women with CHD.

Effect of valsartan on systemic right ventricular function: a double-blind, randomized, placebo-controlled pilot trial.

BACKGROUND: The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated. METHODS AND RESULTS: We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared with placebo in patients with a systemic right ventricle caused by congenitally or surgically corrected transposition of the great arteries. The primary end point was change in right ventricular ejection fraction during 3-year follow-up, determined by cardiovascular magnetic resonance imaging or, in patients with contraindication for magnetic resonance imaging, multirow detector computed tomography. Secondary end points were change in right ventricular volumes and mass, Vo(2)peak, and quality of life. Primary analyses were performed on an intention-to-treat basis. A total of 88 patients (valsartan, n=44; placebo, n=44) were enrolled in the trial. No serious adverse effects occurred in either group. There was no significant effect of 3-year valsartan therapy on systemic right ventricular ejection fraction (treatment effect, 1.3%; 95% confidence interval, -1.3% to 3.9%; P=0.34), maximum exercise capacity, or quality of life. There was a larger increase in right ventricular end-diastolic volume (15 mL; 95% confidence interval, 3-28 mL; P<0.01) and mass (8 g; 95% confidence interval, 2-14 g; P=0.01) in the placebo group than in the valsartan group. CONCLUSIONS: There was no significant treatment effect of valsartan on right ventricular ejection fraction, exercise capacity, or quality of life. Valsartan was associated with a similar frequency of significant clinical events as placebo. Small but significant differences between valsartan and placebo were present for change in right ventricular volumes and mass. CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN52352170.

Uteroplacental blood flow, cardiac function, and pregnancy outcome in women with congenital heart disease.

BACKGROUND: Pregnant women with congenital heart disease (CHD) are susceptible to cardiovascular, obstetric, and offspring complications. In women with CHD, cardiac dysfunction may compromise uteroplacental flow and contribute to the increased incidence of obstetric and offspring events. METHODS AND RESULTS: We performed a prospective multicenter cohort study of pregnant women with CHD and healthy pregnant women. We compared clinical, laboratory, echocardiographic, and uteroplacental Doppler flow (UDF) parameters at 20 and 32 weeks gestation, and pregnancy outcome. We related cardiovascular parameters to UDF parameters and pregnancy outcome in women with CHD. We included 209 women with CHD and 70 healthy women. Cardiovascular parameters (N-terminal pro-B-type natriuretic peptide, left and right ventricular function) differed between both groups. UDF parameters were impaired in CHD women (umbilical artery pulsatility and resistance index at 32 weeks in CHD versus healthy women, P=0.0085 and P=0.017). The following cardiovascular parameters prepregnancy and at 20 weeks gestation were associated with UDF (umbilical artery resistance index) at 32 weeks at multivariable analysis: (1) right ventricular function (tricuspid annular plane systolic excursion) (P=0.002), (2) high N-terminal pro-B-type natriuretic peptide (P=0.085), (3) systemic (P=0.001), and (4) pulmonary (P=0.045) atrioventricular valve regurgitation. Women with CHD had more obstetric (58.9% versus 32.9%, P<0.0001) and offspring events (35.4% versus 18.6%, P=0.008) than healthy women. Impaired UDF was associated with adverse obstetric and offspring outcome. CONCLUSIONS: UDF parameters are abnormal in pregnant women with CHD. Cardiovascular function is associated with an abnormal pattern of UDF. Compromised UDF may be a key factor in the high incidence of offspring and obstetric complications in this population.

Exercise training improves exercise capacity in adult patients with a systemic right ventricle: a randomized clinical trial.

OBJECTIVE: To assess whether exercise training in adult patients with a systemic right ventricle (RV) improves exercise capacity and quality of life and lowers serum N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels. DESIGN: Multi-centre parallel randomized controlled trial. PARTICIPANTS: Patients with a systemic RV due to congenitally or surgically corrected transposition of the great arteries. METHODS: Fifty-four adult patients with a systemic RV, were randomized using unmarked opaque envelopes to an intervention group (n = 28) with three training sessions per week for 10 consecutive weeks, and a control group (n = 26). Randomization was stratified by participating centre. At baseline, and follow-up, we determined maximal exercise capacity (V'O(2peak)), serum NT-proBNP levels, and quality of life by means of the SF-36, and the TAAQOL Congenital Heart Disease questionnaires. The final analysis was performed by linear regression, taking into account the stratified randomization. RESULTS: Forty-six patients were analysed (male 50%, age 32 ± 11 years, intervention group n = 24, control group n = 22). Analysis at 10 weeks showed a significant difference in V'O(2peak) (3.4 mL/kg/min, 95% CI: 0.2 to 6.7; P = 0.04) and resting systolic blood pressure (-7.6 mmHg, 95% CI: -14.0 to -1.3; P = 0.03) in favour of the exercise group. No significant changes were found in serum NT-proBNP levels or quality of life in the intervention group or in the control group nor between groups. None of the patients in the intervention group had to discontinue the training programme due to adverse events. CONCLUSION: In adult patients with a systemic RV exercise training improve exercise capacity. We recommend to revise restrictive guidelines, and to encourage patients to become physically active. ( TRIAL REGISTRATION: The study was registered at http://trialregister.nl. Identifier: NTR1909.).

Turning 18 with congenital heart disease: prediction of infective endocarditis based on a large population.

AIMS: The risk of infective endocarditis (IE) in adults with congenital heart disease is known to be increased, yet empirical risk estimates are lacking. We sought to predict the occurrence of IE in patients with congenital heart disease at the transition from childhood into adulthood. METHODS AND RESULTS: We identified patients from the CONCOR national registry for adults with congenital heart disease. Potential predictors included patient characteristics, and complications and interventions in childhood. The outcome measure was the occurrence of IE up to the age of 40 and 60. A prediction model was derived using the Cox proportional hazards model and bootstrapping techniques. The model was transformed into a clinically applicable risk score. Of 10 210 patients, 233 (2.3%) developed adult-onset IE during 220 688 patient-years. Predictors of IE were gender, main congenital heart defect, multiple heart defects, and three types of complications in childhood. Up to the age of 40, patients with a low predicted risk (<3%) had an observed incidence of less than 1%; those with a high predicted risk (≥3%) had an observed incidence of 6%. The model also yielded accurate predictions up to the age of 60. CONCLUSION: Among young adult patients with congenital heart disease, the use of six simple clinical parameters can accurately predict patients at relatively low or high risk of IE. After confirmation in other cohorts, application of the prediction model may lead to individually tailored medical surveillance and educational counselling, thus averting IE or enabling timely detection in adult patients with congenital heart disease.

Pregnancy in women with corrected tetralogy of Fallot: occurrence and predictors of adverse events.

BACKGROUND: In women with corrected tetralogy of Fallot (ToF), pregnancy is associated with maternal cardiac, obstetric, and offspring complications. Our aim is to investigate the magnitude and determinants of pregnancy outcome in women with corrected ToF. METHODS: In this retrospective international multicenter study using 2 congenital heart disease registries, 204 women with corrected ToF were identified. Within this group, 74 women had 157 pregnancies, including 30 miscarriages and 4 terminations of pregnancy. Detailed information on each completed pregnancy (n = 123) was obtained using medical records and supplementary interviews. RESULTS: Cardiovascular events occurred during 10 (8.1%) pregnancies, mainly (supra)ventricular arrhythmias. Obstetric and offspring events occurred in 73 (58.9%) and 42 (33.9%) pregnancies, respectively, including offspring mortality in 8 (6.4%). The most important predictor was use of cardiac medication before pregnancy (odds ratio for cardiac events 11.7, 95% CI 2.2-62.7; odds ratio for offspring events 8.4, 95% CI 1.4-48.6). In pregnancies with cardiovascular events, significantly more small-for-gestational-age children were born (P value < .01). CONCLUSIONS: Cardiovascular, obstetric, and offspring events occur frequently during pregnancies in women with ToF. Maternal use of cardiovascular medication is associated with pregnancy outcome, and maternal cardiovascular events during pregnancy are highly associated with offspring events.

Associations between cardiovascular parameters and uteroplacental Doppler (blood) flow patterns during pregnancy in women with congenital heart disease: Rationale and design of the Zwangerschap bij Aangeboren Hartafwijking (ZAHARA) II study.

BACKGROUND: Previous research has shown that women with congenital heart disease (CHD) are more susceptible to cardiovascular, obstetric, and offspring events. The causative pathophysiologic mechanisms are incompletely understood. Inadequate uteroplacental circulation is an important denominator in adverse obstetric events and offspring outcome. The relation between cardiac function and uteroplacental perfusion has not been investigated in women with CHD. Moreover, the effects of physiologic changes on pregnancy-related events are unknown. In addition, long-term effects of pregnancy on cardiac function and exercise capacity are scarce. METHODS: Zwangerschap bij Aangeboren Hartafwijking (ZAHARA) II, a prospective multicenter cohort study, investigates changes in and relations between cardiovascular parameters and uteroplacental Doppler flow patterns during pregnancy in women with CHD compared to matched healthy controls. The relation between cardiovascular parameters and uteroplacental Doppler flow patterns and the occurrence of cardiac, obstetric, and offspring events will be investigated. At 20 and 32 weeks of gestation, clinical, neurohumoral, and echocardiographic evaluation and fetal growth together with Doppler flow measurements in fetal and maternal circulation are performed. Maternal evaluation is repeated 1 year postpartum. IMPLICATIONS: By identifying the factors responsible for pregnancy-related events in women with CHD, risk stratification can be refined, which may lead to better pre-pregnancy counseling and eventually improve treatment of these women.

Mortality in adult congenital heart disease.

AIMS: Mortality in adults with congenital heart disease is known to be increased, yet its extent and the major mortality risks are unclear. METHODS AND RESULTS: The Dutch CONCOR national registry for adult congenital heart disease was linked to the national mortality registry. Cox's regression was used to assess mortality predictors. Of 6933 patients, 197 (2.8%) died during a follow-up of 24 865 patient-years. Compared with the general national population, there was excess mortality, particularly in the young. Median age at death was 48.8 years. Of all deaths, 77% had a cardiovascular origin; 45% were due to chronic heart failure (26%, age 51.0 years) or sudden death (19%, age 39.1 years). Age predicted mortality, as did gender, severity of defect, number of interventions, and number of complications [hazard ratio (HR) range 1.1-5.9, P < 0.05]. Several complications predicted all-cause mortality beyond the effects of age, gender, and congenital heart disease severity, i.e. endocarditis, supraventricular arrhythmias, ventricular arrhythmias, conduction disturbances, myocardial infarction, and pulmonary hypertension (HR range 1.4-3.1, P < 0.05). These risks were similar in patients above and below 40 years of age. Almost all complications predicted death due to heart failure (HR range 2.0-5.1, P < 0.05); conduction disturbances and pulmonary hypertension predicted sudden death (HR range 2.0-4.7, P < 0.05). CONCLUSION: Mortality is increased in adults with congenital heart disease, particularly in the young. The vast majority die from cardiovascular causes. Mortality risk, particularly by heart failure, is increased by virtually all complications. Complications are equally hazardous in younger as in older patients.

Predictors of pregnancy complications in women with congenital heart disease.

AIMS: Data regarding pregnancy outcome in women with congenital heart disease (CHD) are limited. METHODS AND RESULTS: In 1802 women with CHD, 1302 completed pregnancies were observed. Independent predictors of cardiac, obstetric, and neonatal complications were calculated using logistic regression. The most prevalent cardiac complications during pregnancy were arrhythmias (4.7%) and heart failure (1.6%). Factors independently associated with maternal cardiac complications were the presence of cyanotic heart disease (corrected/uncorrected) (P < 0.0001), the use of cardiac medication before pregnancy (P < 0.0001), and left heart obstruction (P < 0.0001). New characteristics were mechanical valve replacement (P = 0.0014), and systemic (P = 0.04) or pulmonary atrioventricular valve regurgitation related with the underlying (moderately) complex CHD (P = 0.03). A new risk score for cardiac complications is proposed. The most prevalent obstetric complications were hypertensive complications (12.2%). No correlation of maternal characteristics with adverse obstetric outcome was found. The most prevalent neonatal complications were premature birth (12%), small for gestational age (14%), and mortality (4%). Cyanotic heart disease (corrected/uncorrected) (P = 0.0003), mechanical valve replacement (P = 0.03), maternal smoking (P = 0.007), multiple gestation (P = 0.0014), and the use of cardiac medication (P = 0.0009) correlated with adverse neonatal outcome. CONCLUSION: In our tertiary CHD cohort, cardiac, obstetric, and neonatal complications were frequently encountered, and (new) correlations of maternal baseline data with adverse outcome are reported. A new risk score for adverse cardiac complications is proposed, although prospective validation remains necessary.

Bleeding and thrombotic risk in pregnant women with Fontan physiology.

BACKGROUND/OBJECTIVES: Pregnancy may potentiate the inherent hypercoagulability of the Fontan circulation, thereby amplifying adverse events. This study sought to evaluate thrombosis and bleeding risk in pregnant women with a Fontan. METHODS: We performed a retrospective observational cohort study across 13 international centres and recorded data on thrombotic and bleeding events, antithrombotic therapies and pre-pregnancy thrombotic risk factors. RESULTS: We analysed 84 women with Fontan physiology undergoing 108 pregnancies, average gestation 33±5 weeks. The most common antithrombotic therapy in pregnancy was aspirin (ASA, 47 pregnancies (43.5%)). Heparin (unfractionated (UFH) or low molecular weight (LMWH)) was prescribed in 32 pregnancies (30%) and vitamin K antagonist (VKA) in 10 pregnancies (9%). Three pregnancies were complicated by thrombotic events (2.8%). Thirty-eight pregnancies (35%) were complicated by bleeding, of which 5 (13%) were severe. Most bleeds were obstetric, occurring antepartum (45%) and postpartum (42%). The use of therapeutic heparin (OR 15.6, 95% CI 1.88 to 129, p=0.006), VKA (OR 11.7, 95% CI 1.06 to 130, p=0.032) or any combination of anticoagulation medication (OR 13.0, 95% CI 1.13 to 150, p=0.032) were significantly associated with bleeding events, while ASA (OR 5.41, 95% CI 0.73 to 40.4, p=0.067) and prophylactic heparin were not (OR 4.68, 95% CI 0.488 to 44.9, p=0.096). CONCLUSIONS: Current antithrombotic strategies appear effective at attenuating thrombotic risk in pregnant women with a Fontan. However, this comes with high (>30%) bleeding risk, of which 13% are life threatening. Achieving haemostatic balance is challenging in pregnant women with a Fontan, necessitating individualised risk-adjusted counselling and therapeutic approaches that are monitored during the course of pregnancy.

Rationale and design of a trial on the effect of angiotensin II receptor blockers on the function of the systemic right ventricle.

BACKGROUND: Angiotensin II receptor blockers have been proven to be beneficial in left ventricular failure. In patients with a morphologic right ventricle supporting the systemic circulation, its efficacy has not yet been established. METHODS: We designed a multicenter, prospective, randomized, double-blind, placebo-controlled trial studying the effect of valsartan in patients with a systemic right ventricle due to a congenitally or surgically corrected transposition of the great arteries. The primary end point is the change in right ventricular ejection fraction as measured by cardiovascular magnetic resonance or multidetector row cardiac computed tomography in case of pacemaker patients. CONCLUSION: This large prospective, double-blind, randomized, placebo-controlled trial will establish the role of angiotensin II receptor blockers (valsartan) in the treatment of patients with a systemic right ventricle.